Abstract
INTRODUCTION: It is unknown whether biomarkers of neurodegeneration collected from dried blood spots (DBS) in large-scale population settings are useful in predicting cognitive decline many years later. METHODS: In 2015, we collected DBS of 13,679 individuals aged 58 and older. All DBS were assayed for ApoE4 protein, and a smaller subsample for pTau217, GFAP, and NfL. In 2022, we obtained detailed cognition measures for 6,523 respondents. Regression analyses tested the likelihood of cognitive impairment as a function of biomarker levels. RESULTS: Respondents with ApoE4 detection have worse cognitive performance seven years later as measured by six different cognitive performance measures (p<0.001). The combination of all four biomarkers is a statistically significant predictor for five cognitive performance measures, with pTau217 having the most systematic association. DISCUSSION: DBS-based biomarkers of neurodegeneration provide a cost-efficient and scalable early warning signal enabling preventive measures against AD/ADRD before the onset of serious symptoms.